Michigan Prostate SPORE 2025-2030

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

Linked publications & trials

Abstract

Since its inception in 1995, the Michigan Prostate SPORE has harnessed the extensive intellectual and physical resources of the University of Michigan (U-M) community to reduce the morbidity and mortality associated with prostate cancer (PCa). The program supports an interactive group of basic and clinical investigators engaged in translational research, leading to significant advancements in the diagnosis, prevention, and treatment of PCa. Key achievements from the most recent grant period include: 1) Retrospective characterization of CDK12- mutant PCa's clinical behavior (Eur. Urol., 2020) and completion of the IMPACT clinical trial assessing immune checkpoint blockade in CDK12-altered metastatic PCa (Clin. Cancer Res., 2024). 2) Development of Cdk12 knockout mice (Cell Rep. Med., 2024) and CDK12/13 PROTAC degraders (J. Med. Chem., 2022) to investigate the role of CDK12 in PCa. 3) Clinical validation of the urinary MyProstateScore 2.0 (MPS2) multiplex QRT-PCR assay, based on TMPRSS2-ERG, PCA3, and 16 transcripts associated with aggressive PCa (JAMA Onc., 2024). 4) Development and evaluation of over 50 new androgen receptor (AR) PROTAC degraders (Neoplasia, 2020; J. Med. Chem., 2021). These translational research efforts are bolstered by horizontal and vertical collaborations with numerous institutions, resources, and biotech companies, including the University of Washington, National Cancer Institute Early Detection Research Network, Michigan Urological Surgery Improvement Collaborative, Canary PCa Active Surveillance Study, Lynx Dx, Esanik Therapeutics, RAAPTA Therapeutics, and Aurigene Oncology. We also continue to partner with the Karmanos Cancer Institute (KCI) in this application as a collaborating clinical site, allowing the SPORE to leverage the diverse patient populations of both institutions, including an underserved demographic at KCI. This application introduces three new projects: Project 1: Targeting PIKfyve-driven lipid homeostasis as a metabolic vulnerability in neuroendocrine PCa (NEPC). Here we identify the lipid kinase PIKfyve as a therapeutic target for NEPC. Project 2: Validation and clinical utility of a multiplex urine biomarker for identifying clinically significant PCa, focusing on a clinical utility trial for MPS2. Project 3: Development of serine/threonine phosphatase PP2A molecular glues for the treatment of advanced PCa, creating first-in-class PP2A molecular glues for PCa. These projects are supported by an ongoing institutional commitment of funding and space, successful Career Development and Developmental Research Programs, and three cores: Administrative, Biostatistics/Bioinformatics, and Biospecimen/Pathology. The Michigan Prostate SPORE continues to prioritize rigorous scientific review of its translational research programs, the collaboration of basic and clinical investigators, leveraging expertise from within and outside the PCa field, and maintaining flexibility to fund promising new research approaches.